The proposed Harvard/Brigham and Women's Hospital Skin Disease Research Core Center (HSDRC) will unite under a single aegis the talents and skills of 36 Investigators and Consultants from the Brigham and Women's Hospital, Harvard Medical School, Harvard School of Public Health, Children's Hospital Medical Center, Dana Farber Cancer Institute, the Center for Blood Research, and Massachusetts General Hospital. Research strengths of HSDRC members are diverse and fall into the general categories of Immunology, Inflammation, and Infectious Disease, and Cell Biology, Cancer Biology, and the Cytoskeleton. HSDRC investigators, based in multiple divisions and departments, will share a common goal of understanding the fundamental mechanisms of skin disease through novel and innovative scientific approaches. Core Facilities have been created to facilitate these approaches. A "Transgenic Models of Skin Disease" core will permit the efficient generation, propagation, and experimental analysis of transgenic mice that show either tissue-specific transgene overexpression or targeted gene deletions relevant to skin disease. A "Morphology and Cell Analysis" core will utilize light and electron microscopy and flow cytometry, with nucleic acid and antibody probes, to analyze both human and murine cutaneous cells and tissue. A Cell Culture core will provide investigators with cultured normal and transformed skin cells, as well as develop new methods to culture cutaneous cells of human and murine origin. Pilot and Feasibility studies, principally from promising young investigators with guidance from established investigators, reflect the depth of the Research Base. The first round of P and F studies have been chosen to complement each other and to foster collaborative interactions between groups that have not previously interacted scientifically in the study of skin diseases. Two studies use unique mice created by targeted gene knockout approaches (E-selectin and B7) to study the role of these molecules in cutaneous pathology. Two other studies use another unique gene knockout mouse (RAG-2) that lacks a functional immune system as human skin graft recipients to study, respectively, the role of human Langerhans cells in HIV transmission and human T cell-epidermal interactions. Other studies use a unique transgenic approaches to ablate cutaneous mast cells and target E-cadherin expression to T cells. A final study compares immunologic events in human cutaneous lupus with a murine lupus model. The first round of P and F studies were intentionally selected to encourage principal investigators to interact and share data and insights. The goals of the HSDRC are to foster collaborations and interactions between investigative dermatologists and other biomedical scientists, and to provide education, enlightenment, training, and scientific innovation that will positively affect the achievement of our shared goal to understand and successfully treat skin disease.